Barbital-induced changes in sensitivity to the behavioral effects of narcotics.

Twelve male (Spraque-Dawley) rats were trained to respond under a variable-interval 15 sec schedule of sweetened-milk reinforcement. Rats were tested with doses of morphine and methadone, both before and after the development of tolerance to barbital (100 mg/kg, IP). Barbital-tolerant rats were tolerant to the effects of methadone on VI responding but were not tolerant to the effects of morphine. These data demonstrate that tolerance to some narcotics can develop after chronic exposure to drugs other than those of the same pharmacologic class. Furthermore, this investigation demonstrates the necessity of considering changes in the pharmacokinetics of a narcotic as a possible explanation for the development of tolerance to the behavioral effects of the drug.